Table 1.

Current and future targets of disease modifying therapies for Alzheimer’s disease

Decrease Aβ production – β-secretase inhibition – γ-secretase inhibition or modulation – α-secretase enhancement Decrease Aβ aggregation – Decrease metal ion mediated fibrilization – Decrease oligomer formation via reduction of Aβ monomer – Decrease plaques via blocking β-pleated sheet formation Increase Aβ degradation – Insulin-degrading enzyme (IDE) activation – Neprilysin activation Increase Aβ clearance – “Active” vaccination with truncated Aβ peptide – Passive immunization with monoclonal antibody against Aβ epitope – Passive immunization with antibody against specific confirmational forms of Aβ (e.g. oligomers, protofibrils, or plaque) Decrease tau and neurofibrillary tangle formation – Prevent tau hyperphosphorylation – Decrease tau aggregation – Stabilize microtubules – Active and passive immunization against tau Neuroprotection and/or Neuroregeneration – Anti-oxidant and other agents to preserve metabolic and/or mitochondrial function – Anti-apoptotic agents – Decrease inflammatory damage – Nerve growth factor enhancement – Stem-cell replacement